The present invention broadly relates to a contraceptive vaccine for a target species of mammals, as well as a methodology for making such a contraceptive vaccine. The vaccine can be applied to a wide range of target species, including, but not limited to, cats and dogs.
Much research has gone into the examination and description of folliculogenesis, oocyte maturation, ovulation, and subsequent fertilization, in many mammalian groups. Historically, research attention focused on the description of normal fertility and how this could be harnessed to maximize reproductive outcome. However, over the past 50 years some considerable effort has gone into the development of methodologies to manipulate the reproductive cycle for the purposes of disrupting reproductive function (i.e., contraception). Such efforts have concentrated on methods to disrupt the normal reproductive cycle through the use of hormonal therapies and, more recently, methodologies to raise antibodies to block fertilization.
Current work seeking to identify contraceptive agents or vaccines has focused on generating antibodies to the zona pellucida, the outer covering of mammalian eggs. In particular, zona pellucida vaccines have been developed from pigs' eggs. These vaccines have been used in a number of animal species including for example, the horse, buffalo, elephant, bear, elk and sheep. In some of these species, namely the horse, bear, elephant and elk, this vaccine has demonstrated excellent results in preventing pregnancy, while in others it has been less successful, with results being particularly dismal in the dog and cat. It is of considerable interest as to why animal species respond so differently to the zona pellucida vaccine.
The present inventors believe that the zona pellucida vaccine does not work totally through the mechanism of blocking fertilization (as was originally hypothesized), but also has a direct role in blocking folliculogenesis, oocyte maturation, and ovulation. They believe that an immune cross reactivity of the zona pellucida antibodies to granulosa cells and/or ovarian stromal cells occurs during maturation of the ovum. The inventors contend that the zona pellucida vaccine, as currently being produced, generates a low immune cross reactivity to granulosa cells and/or ovarian stromal cells and, as such, is capable of blocking the fertilization of a few (one or two) ovulatory oocytes as well as partially interfering with folliculogenesis and ovarian function. Studies have shown that mares given two or three injections of the zona pellucida vaccine show reversible infertility, while multiple and repeated injections of the zona pellucida vaccine in mares leads to sustained antibody production and permanent infertility (Kirkpatrick, J F, Liu, I K M, Turner, J W, Jr., Naugle R, Keiper R, Long-term effects of porcine zona pellucida immunocontraception on ovarian function in feral horses (Equus caballus). J Rerod Fertil 1992 (94): 437-444). This leads to the conclusion that the zona pellucida vaccine has an effect on the ovaries themselves. Further support for this is the fact that oophoritis and abnormal cyclicity are consistent findings in multi-fecund species such as dogs and mice when zona pellucida is tested as a potential contraceptive vaccine. Low immunogenicity of the zona pellucida vaccine is demonstrated by its' success at blocking fertilization in low-fecund species (e.g., the horse, buffalo, sheep, elephant and bear) but less success in fully blocking ovarian function, folliculogenesis and fertilization in multi-fecund species (e.g., the dog and cat).
Accordingly, it would be desirable to develop a non-surgical sterilant or contraceptive vaccine that will be effective for most, if not all, eutherian mammals, including the cat and the dog.